FDA Grants Priority Review for Glasdegib in Patients With Previously Untreated AML


The U.S. Food and Drug Administration (FDA) recently accepted a new drug application and granted Priority Review designation for glasdegib, an investigational oral smoothened inhibitor being evaluated for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose cytarabine. The Prescription Drug User Fee Act goal date for a decision by the FDA is in December 2018.

“Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival,” said Mace Rothenberg, MD, Chief Development Officer, Oncology, Pfizer Global Product Development. “In an investigational phase II study, glasdegib in combination with low-dose cytarabine showed a significant improvement in overall survival compared to patients who received low-dose cytarabine alone....”


The submission is based on results from the phase II BRIGHT 1003 study, a randomized, open-label, multicenter trial investigating glasdegib combined with low-dose cytarabine (n = 88) vs low-dose cytarabine alone (n = 44) in 132 patients with previously untreated AML or high-risk myelodysplastic syndrome who were not eligible for intensive chemotherapy. Results demonstrated a significant improvement in the primary endpoint of overall survival.

Median overall survival was 8.8 months for patients treated with glasdegib plus low-dose cytarabine compared with 4.9 months for patients treated with low-dose cytarabine only. This difference represented a 49.9%  reduction in the risk of death for patients treated with glasdegib plus low-dose cytarabine (hazard ratio = 0.501, 95% confidence interval = 0.334–0.752, one-sided P = .0003). The BRIGHT 1003 results were presented in 2016 at the 58th American Society of Hematology Annual Meeting.

The most frequently reported (≥ 30% of patients) adverse events in patients treated with glasdegib plus low-dose cytarabine compared to low-dose cytarabine alone were anemia (45% vs 42%), febrile neutropenia (36% vs 27%), nausea (36% vs 12%), decreased appetite (32% vs 12%), fatigue (31% vs 20%), and thrombocytopenia (30% vs 27%). The most frequently reported (≥ 15% of patients) serious adverse events for patients treated with glasdegib plus low-dose cytarabine compared to low-dose cytarabine alone were febrile neutropenia (29% vs 20%) and pneumonia (21% vs 17%).

About Glasdegib

Glasdegib is an investigational, oral, once-daily therapy that is thought to inhibit the smoothened receptor, thereby disrupting the Hedgehog pathway. Abnormal Hedgehog pathway activation is thought to play a role in the development of multiple types of cancers, including solid tumors and hematologic malignancies. It has not received regulatory approval in any country.

The phase III BRIGHT AML 1019 trial, which is evaluating the addition of glasdegib to intensive or nonintensive chemotherapy in patients with newly diagnosed AML, began enrolling earlier this year.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




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